Percent mammographic destiny (PMD) reflects breast tissue composition, is a strong risk factor for breast cancer and may account for a substantial proportion of the disease. The mechanism by which PMD influences risk of breast cancer is however unknown. We summarize the evidence that PMD reflects the relative quantities of epithelial, stromal and fat tissues in the breast. We examine the relationship between PMD, these breast tissues, and risk of breast cancer using the 2-stage model of carcinogenesis of Moolgavkar et al as a framework. In this model normal epithelial cells undergo a mutation to become intermediate cells that, after further mutation, become malignant cells.
We review the evidence that during carcinogenesis, the size of the epithelial cell population, and all components of the breast stroma, including collagen, fibroblasts, mesenchymal cells, and the extracellular matrix, possess biological properties that may promote the transition of normal epithelial cells to malignant cells. These findings give rise to testable hypotheses concerning the etiology of breast cancer associated with PMD, and to potential approaches to breast cancer prevention.